Parvovirus B19 infection in pediatric transplant patients.

Evidence of recent parvovirus virus infection (as determined by the presence of a positive IgM antibody titer) without other identified causes of anemia was found in 5 of 26 pediatric solid-organ transplant recipients evaluated for moderate-to-severe anemia between June 1990 and July 1991. Anemia tended to be chronic (median duration of anemia at the time of diagnosis was 12 weeks) and was associated with normal red blood cell indices in the absence of reticulocytes. The median age of the children at the time of presentation with anemia due to parvovirus was 1.8 years at a median time of 8 months after transplantation. Four of the 5 children were treated with i.v. immunoglobulin because of persistence of anemia requiring blood transfusions. A response characterized by an increase in reticulocyte count and normalization of hemoglobin was seen in each of these patients 2-4 weeks after treatment. The remaining patient experienced a spontaneous recovery from her anemia. Parvovirus infection should be included in the differential diagnosis of solid-organ transplant recipients presenting with severe anemia associated with low or absent reticulocytes.

Long-term use of cyclosporine in liver recipients. Reduction of dosages in the first year to avoid nephrotoxicity.

Cyclosporine is a potent immunosuppressive drug, which has dose-related nephrotoxicity. In renal transplantation, the differentiation between rejection and toxicity is difficult and even with the aid of blood levels of the drug, it may be difficult to establish a chronic maintenance dose. Long-term survivors after liver transplantation can provide modes with which to establish maintenance doses, as these are dictated by nephrotoxicity in these patients. Twenty-nine liver transplant patients who survived one year or more were followed for changes in their cyclosporine doses. Daily oral cyclosporine dose, BUN, serum creatinine and bilirubin were monitored. The reductions in cyclosporine were dictated almost entirely by the findings of nephrotoxicity.

Pregnancy after liver transplantation under tacrolimus.

BACKGROUND: The maternal and fetal risk of pregnancy after organ transplantation under tacrolimus has not been reported. This was prospectively studied in 27 pregnancies by 21 female liver recipients who were treated with tacrolimus before and throughout gestation. METHOD: Twenty-seven babies were born between October 1990 and April 1996. In 15 cases, samples were obtained at or after delivery and stored (-40 degrees C) for comparison of tacrolimus concentration in the maternal blood with different combinations of cord and infant venous blood, breast milk, or a section of the placenta. RESULTS: The 21 mothers had surprisingly few serious complications of pregnancy and no mortality. Two infants with 23 and 24 weeks gestation died shortly after birth. The mean birth weight of the other 25 was 2638+/-781 g after a gestational period of 36.6+/-3.3 weeks. Mean birth weight percentile for gestational age was 50.2+/-26.2 (median 40). On the day of delivery, the mean tacrolimus concentrations (ng/ml) were 4.3 in placenta versus 1.5, 0.7, and 0.5 in maternal, cord, and child plasma, and 0.6 in the first breast milk specimens. The infants had a 36% incidence of transient perinatal hyperkalemia (K+>7.0 meq/L) and a mild reversible renal impairment, which were thought to reflect in part maternal homeostasis. One newborn had unilateral polycystic renal disease (the only anomaly). All 25 babies have had satisfactory postnatal growth and development with a current mean weight percentile of 62+/-37 (median 80). CONCLUSIONS: Pregnancy by postliver transplant mothers under tacrolimus was possible with a surprisingly low incidence of the hypertension, preeclampsia, and other maternal complications historically associated with such gestations. As in previous experience with other immunosuppressive regimens, preterm deliveries were common. However, prenatal growth for gestational age and postnatal infant growth for postpartum age were normal.

Water intoxication in normal infants: role of antidiuretic hormone in pathogenesis.

Eight infants, 2 to 5 months of age, who were seen somnolence or irritability, seizures, and hypothermia are described. The symptoms developed following the ingestion of dilute formula. All infants were hyponatremic. Three patients were identified by the symptom complex and were evaluated prior to any therapeutic intervention. Plasma arginine vasopressin concentration and urinary osmolality were either normal or increased despite hyponatremia and decreased serum osmolality. These data, coupled with rapid biochemical and clinical improvement following fluid restriction and/or administration of 3% NaCl, strongly implicate the excessive release of arginine vasopressin in the pathogenesis of this syndrome of water intoxication.

Lumbar cutaneous hemangiomas as indicators of tethered spinal cords.

Children with cutaneous hemangiomas in the lumbar region often also have tethered spinal cords. This diagnosis can be overlooked, because children with cutaneous hemangiomas may be otherwise asymptomatic and neurologically normal. From 1983 to 1987, six consecutive children with lumbar cutaneous hemangiomas underwent magnetic resonance imaging, and a seventh had a myelogram. In all seven children, despite their normal neurologic status, tethered spinal cords were diagnosed. All children had operations, which confirmed this finding. None had postoperative neurologic deficits. Infants and children with similar lumbar cutaneous hemangiomas should have magnetic resonance scans to detect the presence of tethered spinal cords.

Munchausen syndrome by proxy: a new complication of central venous catheterization.

A recent case of supposed gastrointestinal (GI) bleeding in a small child underscored the difficulty inherent in making the diagnosis of Munchausen syndrome by proxy. In this case, an indwelling Broviac central venous catheter was used by the mother to withdraw blood which was then arranged to feign blood loss from her son's upper and lower GI tract. Despite the mother/perpetrator's displaying the classic personality traits of Munchausen syndrome by proxy, diagnosis was not made for many weeks.

Varicella in pediatric orthotopic liver transplant recipients.

From May 1981 to May 1984, 90 pediatric patients underwent liver transplantation and 65 patients survived as of May 1986. Two of the nonsurvivors died with complications related to clinical varicella. Of these 67 patients (65 survivors and two nonsurvivors who died of varicella-related causes), 51 patients were determined to be varicella susceptible. Clinical disease developed in no patients with serologic evidence or clinical history of varicella prior to transplantation. Eighteen susceptible patients were exposed and received zoster immune globulin and varicella did not develop. Clinical disease developed in eight patients despite zoster immune globulin, although one patient received it 96 hours after exposure. Six patients received no zoster immune globulin and clinical varicella developed. In all, varicella developed in 14 patients. Thirteen were admitted to the hospital and treated with intravenous acyclovir. Of those treated, two died of causes related to complications of varicella. The remaining patients treated with acyclovir had mild disease. The one patient not treated with acyclovir also had mild disease. We conclude that patients contracting varicella after liver transplantation while receiving maintenance immunosuppressive agents should be treated with intravenous acyclovir. Generally, when treated with acyclovir while receiving maintenance immunosuppressive drugs, these patients have mild clinical disease. Patients recently treated with high-dose prednisone and cyclosporine may have severe clinical disease resulting in death.

Progression of neurovisceral storage disease with supranuclear ophthalmoplegia following orthotopic liver transplantation.

A 7-year-old girl with progressive ataxia, spasticity, supranuclear ophthalmoplegia, and sea-blue histiocytes in her bone marrow underwent orthotopic liver transplantation for hepatocellular carcinoma. After an initial period of stabilization, she has shown progression of neurologic symptoms with recurrence of storage material in the transplanted liver.

Evaluation of the pediatric patient for liver transplantation.

In a 36-month period from 1981 to 1984, 209 pediatric patients were evaluated for liver transplantation. The purpose of the evaluation was to assess the severity and progression of the disease, anatomical suitability for transplantation, and psychosocial stability and to initiate family education. Of the 209 patients evaluated, 85 (41%) underwent transplantations and 64 (75%) survived at least 12 months. Thirty-four (16%) patients were not considered candidates for transplantation. The mean waiting period increased from 80.3 days to 232 days. Of 174 patients considered for transplantation, 41 (24%) died prior to surgery. A formal evaluation for liver transplantation permitted appropriate selection of candidates and provided education for informed consent. We also stress the need for greater participation in pediatric organ donation.

Changes in life-style after liver transplantation.

Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in life-style. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pretransplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients' behavior significantly improved according to parents' perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents' perceptions of behavior of children appear to be improved after liver transplantation.

Acute profound dystonia in infants with glutaric acidemia.

Acute profound dystonia developed in three previously well infants who were found to have glutaryl-CoA dehydrogenase deficiency in cultured skin fibroblasts. Two patients had excessive urinary excretion of glutaric acid, but one did not. Neuroradiologic studies performed in all three patients at the onset of their illnesses revealed large CSF-containing spaces both within the sylvian fissures and anterior to the temporal lobes. Pathologic examination of the brain of one patient demonstrated cerebral and cerebellar atrophy, shrinkage of the putamen, and white matter vacuolation. Glutaric acidemia may be a common cause of acquired persistent dystonia or choreoathetosis in infancy.

Orthotopic liver transplantation in children: two-year experience with 47 patients.

During a 24-month period (May 1981 to May 1983), 47 pediatric patients (ranging in age from 7 months to 18 years) underwent orthotopic liver transplantation using cyclosporine and prednisone. Major indications were biliary atresia/hypoplasia, and metabolic liver disease. Thirty-two of 138 patients evaluated for the procedure died prior to transplantation. Thirty patients are alive from 6 to 29 months later including 7/15 patients who required retransplantation. Twenty-one of 32 patients are alive at 1 year following initial transplantation. All 30 survivors are clinically well and living at home; only one has an abnormal bilirubin level. Serious, life-threatening medical and surgical complications were common during the early months following transplantation. With one exception, deaths and major rejection episodes occurred early (before 120 days). All survivors are relieved of the stigmata of chronic liver disease, and many have demonstrated catch-up growth. Liver transplantation is an effective treatment for end-stage pediatric liver disease.

Echocardiographic findings before and after liver transplantation.

Echocardiographic studies were performed in 73 patients with various types of chronic liver disease. They were 0.5 to 19 years old (mean 5). Thirteen patients underwent follow-up echocardiography 1 to 13 months (mean 6) after liver transplantation. Preoperatively 60 patients (82%) showed evidence of high cardiac output (cardiac index greater than 4 liters/min/m2); these patients manifested increased left ventricular (LV) and left atrial dimensions and a thickened LV posterior wall. Transvenous contrast echocardiographic study confirmed the presence of intrapulmonary arteriovenous shunting in 4 patients. Studies after liver transplantation revealed a reduced LV end-diastolic dimension in 12 patients. Cardiac index was reduced a mean of 35% after transplantation (p less than 0.001). This study suggests that liver transplantation improves common hemodynamic abnormalities in chronic liver disease.

Fatal pulmonary aspergillosis presenting as acute eosinophilic pneumonia in a previously healthy child.

A previously healthy boy presented with cough and diffuse pulmonary interstitial infiltrates. Acute eosinophilic pneumonia was diagnosed by bronchoalveolar lavage in the absence of a demonstrable infectious etiologic agent. Corticosteroid therapy resulted in immediate improvement but was followed by respiratory distress and death from invasive aspergillosis and Pseudomonas cepacia sepsis.

Cyclosporine absorption following orthotopic liver transplantation.

Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intravenous cyclosporine study was performed following an average dose of 2.1 mg/kg. The patients were again studied when they received the same intravenous dose plus an oral dose of cyclosporine of 8.6 mg/kg or an oral dose alone. Blood samples were collected and analyzed for cyclosporine using high-performance liquid chromatography. Cyclosporine blood clearance ranged from 29 to 203 mL/min (1.9-21.5 mL/min/kg) in children and from 253 to 680 mL/min (3.2-7.6 mL/min/kg) in adults. The mean cyclosporine clearance value was 9.3 mL/min/kg in the pediatric patients and 5.5 mL/min/kg in the adults. Cyclosporine bioavailability was less than 5% in six studies on five pediatric patients in the immediate postoperative period. The bioavailability varied from 8% to 60% in adult liver transplant patients (mean, 27%). We conclude that: cyclosporine clearance is highly variable between patients, pediatric patients clear the drug more rapidly than adults and therefore need a higher cyclosporine dose on a body weight basis, cyclosporine is poorly and variably absorbed in liver transplant patients, and cyclosporine blood concentration monitoring is essential following orthotopic liver transplantation.

Pediatric liver transplantation: patient evaluation and selection, infectious complications, and life-style after transplantation.

Liver transplantation is an increasingly accepted treatment for children with end-stage liver disease. Evaluation of the patient and appropriate patient selection for transplantation will become increasingly important issues as more and more children come to transplantation and compete for available organs. Numerous complications occur after transplantation, including infections. We have summarized our experience with bacterial, fungal, and viral infections in these patients and emphasize the need for continued improvement in immune suppressive drugs and regimens to minimize such complications. And finally, information presented on 65 pediatric patients followed 2 to 5 years suggests that, despite numerous complications and often prolonged hospitalization for transplantation, life-style after transplantation appears to be significantly improved.

The intraoperative medical management of childhood pheochromocytoma.

The intraoperative medical management of eight children, ages 6--15 yr, with familial benign pheochromocytoma is described. All patients received a standardized regimen of alpha- and beta-adrenergic blocking drugs during a preoperative period ranging from 5 to 20 days. In six patients, all symptoms, including diaphoresis, palpitations and hypertension became well-controlled and the operative course was uneventful. In two others the cardiovascular symptoms persisted despite gradual increases in the above medications; in these two patients, the addition of sodium nitroprusside resulted in satisfactory titration of blood pressure and permitted performance of the operation with minimal complications. The specific treatment guidelines used in our patients may reduce the intraoperative complications previously encountered in this tumor.

Hepatic infarction and acute liver failure in children with extrahepatic biliary atresia and cirrhosis.

Acute hepatic failure developed in four patients (aged 7 to 13 months) who had extrahepatic biliary atresia treated initially by portoenterostomy. Two were stable outpatients with minimal jaundice, while the other two were hospitalized for metabolic or nutritional complications. Postmortem examination in each patient revealed massive acute hepatic infarction with few surviving hepatocytes. In all cases, the hepatic failure had been preceded by an episode of hypotension and/or hypovolemia. The exact pathogenesis of the infarction remains unclear but it may be related to decreased hepatic blood flow secondary to biliary obstruction. The only effective treatment for these patients is intensive supportive care and urgent liver transplantation.

Complication of acute epiglottitis.

Acute airway obstruction secondary to supraglottic inflammation is a regional manifestation of epiglottitis in children. Pneumonia, meningitis, cervical adenitis and septic shock are systemic manifestations which can complicate the course of acute epiglottitis. Prompt airway control and institution of appropriate high dose i.v. antibiotics are both important to continue to decrease the morbidity and mortality associated with the regional and systemic manifestations of acute epiglottitis in children.

Pitfalls on the diagnosis of acute osteomyelitis by bone scan.

Two patients with acute osteomyelitis had technetium 99m methylene diphosphonate bone images that were misinterpreted. A review of six prospective evaluations of technetium scanning in the diagnosis of acute osteomyelitis shows that bone image interpretation may be misleading in five to seven per cent of pediatric patients. Definitive diagnostic procedures and management should not be delayed until a positive bone scan is obtained, if the clinical findings are persuasive.